1. Field of the Invention
The present invention relates to hyperbaric chambers and medical treatment methods and systems using hyperbaric chambers. More particularly, the present invention relates to a system and method for using a hyperbaric chamber, a spectrophotometer (preferably a NIRoscope), and an automatic regulating device which receives information from the spectrophotometer to increase the amount of oxygen which gets to the brain of a patient being resuscitated after suffering from, for example, myocardial infarction or cerebral ischemia. The NIRoscope can also be used independently in critical care to monitor aa3 redox ratio or even be broadened to other chromophores in the brain in conjunction with neurology and mental health.
2. General Background of the Invention
Shrinking health care dollars have made the medical profession acutely aware of the enormous cost associated with successful cardiopulmonary resuscitations. (1,2—the parenthetical reference numerals indicate the appropriate article listed in the Appendix). The major expense is related to post-resuscitative care in the hospital, especially the time spent in intensive care. Cost per resuscitation depends on the percentage of survival to hospital discharge and ranges from $550,000 for 0.2% survival to $110,000 for a 10% survival. From a cost analysis perspective, it would be extremely beneficial if the number of survivors could be increased, if their post-resuscitation condition still permitted them to function as independently as possible, and if the post-resuscitation time they spent in the intensive care unit was markedly reduced. For example, it has been shown that by raising the resuscitation success ratio from the present 12% to 20%, there could be a cost savings of approximately $40,000 per patient. (2) According to Virtis (1), of the 3,308,000 patients hospitalized annually, about 1% (330,800) experienced cardiac arrest and were administered CPR. If the current success rate of 12.8% (3) could be raised to 20%, a national health care cost savings of $1.32 billion ($40,000×330,000) per year could be realized.
Although oxygen is considered to be the most important drug used in resuscitation from cardiopulmonary arrest, it is disheartening to learn that for the past 30 years there has been little improvement in resuscitative techniques and that advances in oxygen delivery have not been incorporated to any meaningful extent in resuscitation.
Currently, there are at least two major limitations associated with conventional oxygen delivery: the first pertains to methods of oxygen administration and the second pertains to the unavailability of a reliable, non-invasive, direct or indirect cerebral cortical oxygen monitor that could help assure adequate oxygenation of the brain during CPR. Even under ideal conditions, neither masks nor endotracheal tubes—the techniques currently used for delivering oxygen during resuscitation—deliver sufficient oxygen at sea level (1 atmosphere absolute (atm abs)) for adequate, let alone optimum, oxygen delivery. Therefore, maximum benefit, i.e. maximum recovery of cerebral neurons (minimum residual brain damage) is not attained and, thereby, represents the preeminent reason for the aforementioned dismal results with respect to minimizing brain damage following resuscitation from cardiopulmonary arrest.
What is needed is a system that will provide sufficient oxygen delivery and a sensor for non-invasively measuring in real-time the adequacy of oxygen delivery to the cortical neurons. Hyperbaric oxygen (HBO) provides the means whereby sufficient oxygen could be delivered to the patients. HBO increases the amount of oxygen physically dissolved in the plasma to an extent that greatly supplements that which is carried by hemoglobin in the red blood cells. More importantly, HBO provides for a high partial pressure of oxygen—greater than that which could be attained at sea level—which increases the rate of diffusion of the oxygen into the tissues and cells and helps assure sufficient oxygen to overcome hypoxia and maintain cellular metabolism and integrity. It is this state of oxidative metabolism that lends itself to non-invasive measurement and, thereby, by inference, of adequate tissue and cellular oxygenation. Oxygen also exerts other beneficial physiologic-pharmacologic effects which will prevent or ameliorate the onset of hypoxia-induced cerebral and cardiac pathology.
Increasing the partial pressure of oxygen inhaled during resuscitative procedures (pressures of oxygen that can be obtained only by hyperbaric oxygen therapy (HBOT)) is expected to be pivotal in improving the success ratio of resuscitation. Such anticipation is to be expected because of the documented beneficial effects of HBOT:                1. HBOT has been suggested as an indicator for identifying potentially good resuscitative candidates. Holbach (4) reported that if patients with cerebral ischemic damage responded well to an initial exposure to HBOT they would continue to improve during post-resuscitative efforts. Patients who did not respond well to the initial HBOT exposure were less likely to recover from ischemic damage.        2. Even after extended periods of cerebral ischemia, resuscitation may be improved by HBOT (5,6)        3. HBOT, when used in conjunction with single photon emission computed tomography (SPECT) (7, 8) using an appropriate radioactive tracer has been shown to help detect the extent of brain injury, identify if there is potentially recoverable brain tissue, and help identify the endpoint of therapy. HBOT is absolutely essential for recovering these neurons.        
To effect successful resuscitations the oxygen dosage must be optimized. Holbach et al. reported that injured brain responds differently to increased pressures of oxygen than does non-injured brain. These investigators demonstrated, based on regional energy utilization, that 1.5 atmospheres absolute (atm abs) of oxygen is optimum for treating injured brain. However, Holbach was not working with resuscitation procedures in which developing and maintaining sufficient cerebral perfusion is critical for delivering oxygen and nutrients to the neurons and for removing end products of metabolism if a successful resuscitation is to be effected.
In injured brain there may be damage to the cerebral circulation thereby disrupting cerebral perfusion. The major limitation of conventional cardiopulmonary resuscitation is the failure to be able to attain and maintain a sufficient cerebral perfusion so as to sustain cardiac and neuronal function.
HBOT represents the most efficient means of supplying sufficient oxygen to tissues (neurons in the brain) thereby reversing hypoxia, sustaining neuronal metabolism, quenching free radicals, decreasing the local formation of acidosis, and stimulating angiogenesis (9). There is no drug currently available that can do what oxygen does in enhancing the survival of injured neurons (10).
It is the contention of the present inventors that real-time monitoring of cellular oxidative states, an indirect but more meaningful measure of tissue oxygen tensions, would help predict whether salvageable tissues are present. Indeed, Sheffield showed that measuring tissue oxygen tensions has been used successfully as a means for predicting which problem wounds would respond to HBOT. Not only does this technique provide predictive value, it also permits following the course of therapy so as to gauge the efficacy of the therapeutic recovery techniques. Thus, from a comparative perspective with respect to the brain, measuring cerebral partial pressure of oxygen (PO2) during resuscitation would be an excellent gauge of successful resuscitative efforts. Waxman et al. used the PO2 in the muscles of the upper arm to judge the success of resuscitation from hypovolemic shock (10). Rivers (11) measured cardiac venous PO2 to predict the return of spontaneous circulation while McCormick (12) measured cerebral venous PO2 to gauge recovery of comatose patients in intensive care. Unfortunately, no one has yet determined what is the real-time, optimal cerebral oxygen tension for tissue recovery, nor does anyone know, using current technology, how to assure that there is optimal oxygen delivery during resuscitation.
Although cerebral neurons are extremely vulnerable to hypoxia, irrespective of its etiology, there have been no reports of direct measurements of cerebral neuronal oxidative states as a means for predicting success of resuscitative efforts. One of the most important reasons for the lack of such knowledge is the absence of reliable, non-invasive instrumentation for measuring cerebral neuronal oxidation-reduction states in humans.
Based on a review of the literature, the present inventors have come to believe that the most promising approach for the non-invasive measurement of cerebral oxidation-reduction states (cerebral PO2) in humans is one based on near infrared (NIR) spectroscopy. Measuring the ratio of cerebral arterial and venous hemoglobin using NIR spectroscopy has been accomplished while individuals were breathing air under 1 atm abs conditions. However, this technology cannot be used under HBOT conditions because the hemoglobin in both the arterial and venous circulations may be completely saturated with oxygen. Instrumentation for measuring the in vivo cytochrome oxidase redox ratio was used successfully in bloodless small animals. (13, 16) However, attempts to apply this technology to blood-profused large animals and humans, Matcher provided inconsistent results. It has been reported the failure to obtain consistency was due to the requirement for a higher gain to detect the cytochrome oxidase redox ratio—there is less cytochrome oxidase than hemoglobin per unit volume of brain tissue and its NIR absorption signal is weaker. It appears that one of the basic problems to be overcome in applying NIR spectroscopy as an aid in resuscitating adult humans is to be able to measure the relatively weak cytochrome oxidase absorption in the presence of a pulsating hemoglobin signal that is 10 times stronger. The effects of varying Hb absorbance, water concentration and tissue light scattering have led to questionable results. (20, 21).
One desideratum for improving resuscitative efforts is a non-invasive instrument with sufficient sensitivity to measure the adequacy of tissue oxygen delivery in real-time at the cellular level so that attending physicians could optimize resuscitative efforts. Such techniques do not have to be quantitative since it is the relative changes in redox levels in real-time that are important.
Recent advances in spectroscopy have made it feasible for appropriate instrumentation to be developed. For example, charged couple device (CCD) spectrophotometers have become more sensitive and can provide absorbance spectra with integration time ranging from 10 msec to 10 seconds. This alone may be adequate to monitor aa3. If not, based on mathematical models using Fourier Transform and deconvolution methods in conjunction with data obtained from a CCD in the near infrared range, the present inventors concluded that an even more sensitive spectrophotometer could be built. In fact, by applying the inventors' algorithm to synthetic (but realistic) cerebral cortex absorption spectra, the redox ratio of cytochrome oxidase can be extracted from the spectra. Furthermore, the result of this analysis shows the real component of the Fourier Transform to be linear to the cytochrome oxidase redox ratio to the fifth decimal place. Such sensitivity should provide the basis for designing instrumentation that is needed for making the necessary measurements of oxidized-reduced cytochrome oxidase ratios in real-time during cardiopulmonary resuscitation. This same technique may be applied to other natural chromophores in the brain such as neuron transmitters or treatment drugs in conjunction with the diagnostics treatment of neurology and psychiatry.
Hyperbaric chambers have long been used for increasing the amount of oxygen supplied to patients suffering from oxygen deprivation. Several articles and patents address this subject. However, it is important to supply the proper amount of oxygen to a patient. Supplying too much can be almost as harmful as supplying too little.
U.S. Pat. Nos. 3,688,770, 3,877,427, and 3,547,118 disclose hyperbaric chambers for oxygenating blood. In U.S. Pat. No. 3,547,118, a regulator automatically controls the relationship between the pressure of the chamber and the pressure of the oxygen supply of a patient in the chamber. U.S. Pat. No. 4,582,055 discloses a similar system.
U.S. Pat. No. 5,220,502 discloses a system for automatically measuring the blood pressure of a patient in a hyperbaric chamber.
U.S. Pat. Nos. 4,281,645; 5,313,941; and 5,873,821 disclose spectrophotometers.
U.S. Pat. Nos. 3,984,673, 4,448,189, and 4,633,859, disclose various apparatus for controlling the environment in hyperbaric chambers.
See also Dalago et al., SU patent document no. 395,091, December 1973; F. G. Hempel et al., “Oxidation of cerebral cytochrome aa3 by oxygen plus carbon dioxide at hyperbaric pressures,”: J. Applied Physiology: Resp.; Env., and Exercise Phys., Vol. 43, No. 5 (November 1977); and S. D. Brown et al., “In vivo binding of carbon monoxide to cytochrome c oxidase in rat brain,” J. Applied Physiology, Vol. 68, No. 2 (February 1990); and U.S. Pat. No. 5,251,632.
All references mentioned herein (and all references to which they refer) are hereby incorporated herein by reference.